Lavendamycin analogs, quinoline-5,8-diones and methods of using them

Abstract

The invention provides novel lavendamycin analogs having the following general formula: ##STR1## and quinoline-5,8-diones having the following formula: ##STR2## Methods of making and using and compositions containing these compounds are also disclosed.

We claim: 
     
       1. A compound having the following formula: ##STR51## wherein, ##STR52## an alkyl, aryl, cycloalkyl, alkynyl, alkenyl or heterocyclic residue, each of which may optionally substituted or unsubstituted, R 1  is a halogen atom,   R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and R 8 , which may be the same or different, each is independently H, a halogen atom, NO 2 , CN, OR 13 , SR 13 , N(R 13 ) 2 , ##STR53## an alkyl, aryl, cycloalkyl, alkenyl, alkynyl, each of which is optionally substituted, ##STR54## an alkyl, cycloalkyl, aryl, alkenyl, alkynyl each of which is optionally substituted,   R 10 , R 11 , and R 13 , which may be the same or different, each is independently H or an alkyl, cycloalkyl, alkenyl, alkynyl, aryl each of which is optionally substituted,   R 12  is H, N(R 11 ) 2 , OR 11 , SR 11 , NR 11  N(R 11 ) 2 , OR 14  N(R 11 ) 2 , or an alkyl, cycloalkyl, aryl, alkenyl, alkynyl each of which is optionally substituted, and   R 14  is an alkylene residue, and or a pharmaceutically acceptable salt thereof.     
     
     
       2. The compound of claim 1 wherein R 1  is Cl. 
     
     
       3. A compound having the following formula: ##STR55## wherein R 1  is a halogen atom, and R 4  is H, a halogen atom, NO 2 , CN, an alkyl, aryl, cycloalkyl, alkenyl, alkynyl, each of which is optionally substituted. 
     
     
       4. The compound of claim 3 wherein R 1  is Cl and R 4  is CH 3 . 
     
     
       5. A composition for treating an animal suffering from cancer comprising an effective amount of a compound of claim 1, 2, 3 or 4 and a pharmaceutically acceptable carrier. 
     
     
       6. The composition of claim 5 wherein the cancer is selected from the group consisting of ovarian, colon, breast, cervical, esophageal, glioblastoma, neuroblastoma, stomach, kidney, skin, lung, pancreatic, seminoma, melanoma, bladder, thyroid, myeloid and lymphoid. 
     
     
       7. A method of treating an animal suffering from cancer comprising administering to the animal suffering from cancer an effective amount of the compound of claim 1, 2, 3 or 4. 
     
     
       8. The method of claim 7 wherein the cancer is selected from the group consisting of ovarian, colon, breast, cervical, esophageal, glioblastoma, neuroblastoma, stomach, kidney, skin, lung, pancreatic, seminoma, melanoma, bladder, thyroid, myeloid and lymphoid. 
     
     
       9. A method of treating HIV infection, comprising administering to an animal suffering from such an infection an effective amount of a compound having the following formula: ##STR56## wherein, ##STR57## an alkyl, aryl, cycloalkyl, alkynyl, alkenyl each of which is optionally substituted, R1, R2, R 3 , R 4 , R 5 , R 6 , R 7 , and R 8 , which may be the same or different, each is independently H, a halogen atom, NO 2 , CN, OR 13 , SR 13 , N(R 13 ) 2 , ##STR58## an alkyl, aryl, cycloalkyl, alkenyl, alkynyl, each of which is optionally substituted, ##STR59## an alkyl, cycloalkyl, aryl, alkenyl, alkynyl each of which is optionally substituted.   R 10 , R 11  and R 13 , which may be the same or different, each is independently H or an alkyl, cycloalkyl, alkenyl, alkynyl, aryl each of which is optionally substituted,   R 12  is H, N(R 11 ) 2 , OR 11 , SR 11 , NR 11  N(R 11 ) 2 , OR 14  N(R 11 ) 2 , or an alkyl cycloalkyl, aryl, alkenyl, alkynyl each of which is optionally substituted, and   R 14  is an alkylene residue, and or a pharmaceutically acceptable salt thereof.     
     
     
       10. The method of claim 9 wherein Y is CO 2  CH 3 , CO 2  H, CO 2  (CH 2 ) 3  CH 3 , CONH 2 , CO 2  CH 2  CH 2  CH(CH 3 ) 2 , or CO 2  (CH 2 ) 7  CH 3 , R 4  is CH 3  or H,   R 6  is H, and   R 10  is CH 3 , or CH 3  (CH 2 ) 2 .   
     
     
       11. A method of treating an animal having a tumor comprising administering to the animal an effective amount of the compound of claims 1, 2, 3 or 4. 
     
     
       12. A compound having the following formula: ##STR60##